System and method of differential pressure control of a reciprocating electrokinetic pump

ABSTRACT

A method of controlling the output of an electrokinetic pump to deliver a target stroke volume includes applying a pump drive signal to the electrokinetic pump for a pump stroke time duration and then determining a volume of a delivery fluid pumped. Then, comparing the volume of the delivery fluid pumped to the target stroke volume; generate a new time interval for applying the pump drive signal. Then apply the pump drive signal to the electrokinetic pump for the new time interval. A system for delivery of fluid includes an electrokinetic pump under the control of an electronic controller. The electronic controller contains computer readable instructions to determine an output of the electrokinetic pump and then generate a stroke time delivery adjustment for precise pumping schemes.

CROSS REFERENCE TO RELATED APPLICATION

This application claims the benefit of priority under 35 U.S.C. §119 to U.S. Provisional Patent Application No. 61/482,960, filed May 5, 2011, and entitled “SYSTEM AND METHOD OF DIFFERENTIAL PRESSURE CONTROL OF A RECIPROCATING ELECTROKINETIC PUMP,” incorporated herein by reference in its entirety.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

FIELD

This application relates to electrokinetic pump control schemes.

BACKGROUND

Precise pumping systems are important for chemical analysis, drug delivery, and analyte sampling. However, traditional pumping systems can be inefficient due to a loss of power incurred by movement of a mechanical piston. Still further, conventional systems may not be configured to compensate for errors during delivery. This is most likely because such pumping systems cannot precisely deliver small amounts of delivery fluid because the mechanical piston cannot be accurately stopped mid-stroke.

Other electrokinetic pumping systems have been described, however, those pumping systems have not included the flow control schemes that take full advantage of partial pump stroke control. In addition, prior pumping systems have not included flow control measurement systems with accuracy sufficient to provide stroke to stroke compensation.

Accordingly, there remains a need for electrokinetic pumping systems with improved flow control schemes.

SUMMARY OF THE DISCLOSURE

In one aspect, there is a method of controlling the output of an electrokinetic pump to deliver a target stroke volume, including applying a pump drive signal to the electrokinetic pump for a pump stroke time duration is about one second; determining a volume of a delivery fluid pumped during the pump stroke time duration; comparing the volume of the delivery fluid pumped to the target stroke volume; generating a new time interval for applying the pump drive signal to the electrokinetic pump based upon the comparing step; and applying the pump drive signal to the electrokinetic pump for the new time interval. In performing the method of controlling the output of an electrokinetic pump the difference between the new time interval and the pump stroke time duration is no more than 100 ms. Alternatively, during the method of controlling the output of an electrokinetic pump and/or the pump stroke time duration is a time duration selected or constrained so as to maintain the electrokinetic pump within the reversible faradaic limits of the electrokinetic pump components or is selected to remain within the reversible faradic operating parameters of the electrokinetic pumps.

In another embodiment, a method of controlling the output of an electrokinetic pump the determining a volume step includes the use of a differential pressure flow technique that may, for example, be based on an input from at least one pressure sensor in communication with the pump outlet or use a flow restrictor and is based on an input from at least one pressure sensor.

In another embodiment, a method of controlling the output of an electrokinetic pump the process of determining a volume step may be based on a comparison of two differential pressure signals after the initial applying a pump drive signal step, be based on an integral a pressure sensor during the applying a pump drive signal step, be based on an integral a difference between two pressure sensors during the applying a pump drive signal step, be based on an estimated delivery condition read from a pressure sensor during the applying a pump drive signal step.

In another embodiment of a method of controlling the output of an electrokinetic pump the duration of the applying a pump drive signal is adjusted based on the estimated delivery condition read from a pressure sensor during the applying a pump drive signal step. In another aspect of a method of controlling the output of an electrokinetic pump the differential pressure flow measurement technique uses input from a pair of pressure sensors. In this aspect of controlling the output of an electrokinetic pump one of the pressure sensors is in communication with the pump outlet or one of the pressure sensors is positioned to indicate backpressure acting on the output of the electrokinetic pump.

In another aspect of a method of controlling the output of an electrokinetic pump, before the applying a pump drive signal for the new time interval, there is a process of applying a pump drive signal of opposite polarity to the pump drive signal used in the initial applying a pump drive signal step. The duration of the applying a pump drive signal of opposite polarity is the same as the pump stroke time duration. In another aspect of controlling the output of an electrokinetic pump after applying the pump drive signal for the new time interval, there is a process of applying a pump drive signal of opposite polarity to the pump drive signal used in the applying a pump drive signal for the new time interval step. The duration of the applying a pump drive signal of opposite polarity is the same as the new time interval duration. During any of the methods of controlling the output of an electrokinetic pump the pump drive signal during the applying steps may be a constant voltage or a constant current.

In another aspect of a control method, the duration of the applying a pump drive signal is adjusted based on the estimated delivery condition read from a pressure sensor just prior to the applying a pump drive signal step. Still further, a method may also decrementing a total volume delivery counter according to the result of the determining a volume of a delivery fluid pumped step or incrementing a total volume delivery counter according to the result of the determining a volume of a delivery fluid pumped step. In one aspect, there is a process of generating a pump stop signal when the result of the determining a volume of a delivery fluid pumped step is the last delivery increment of the total volume delivery counter or is the last delivery decrement of the total volume delivery counter.

There is also provided a system for delivery of fluid having an electrokinetic pump configured to deflect a diaphragm in an outlet chamber, the outlet chamber having an inlet and an outlet. There is also a first check valve in communication with the inlet and a second check valve in communication with the outlet. There is also a pressure sensor positioned to indicate a pressure within the system between the first check valve and the second check valve and computer controller. The computer controller is in communication with the electrokinetic pump and the pressure sensor. The memory of the computer controller or memory accessible to the computer controller contains computer readable instructions to determine an output of the electrokinetic pump based at least in part on a signal from the pressure sensor and to generate a stroke time delivery adjustment after each deflection of the diaphragm into the outlet chamber.

The system may also include another pressure sensor and a flow restrictor wherein, the pressure sensor is positioned to indicate the pressure of the outlet chamber, the flow restrictor is positioned between the outlet chamber outlet and the second check valve and the another pressure sensor is positioned to indicate a pressure within the system between the flow restrictor and the second check valve. The system may also include a reservoir containing a delivery fluid and having an outlet in communication with the outlet chamber inlet. The system may also include a delivery conduit in communication with the outlet chamber outlet. The system may also include a flow restrictor wherein, the flow restrictor is positioned between the outlet chamber outlet and the second check valve and the pressure sensor is positioned to indicate a pressure within the system between the flow restrictor and the outlet chamber. The system may also include another pressure sensor and a flow restrictor wherein, the flow restrictor is positioned between the second check valve and a delivery conduit and the pressure sensor is positioned to indicate the pressure downstream of the flow restrictor in the delivery conduit. The system may also include a user input device in communication with the computer controller wherein the computer controller is adapted and configured to provide and receive signals from the user input device.

In still another aspect of a method of controlling the output of an electrokinetic pump, the difference between the new time interval and the pump stroke time duration is between 4 ms and 64 ms. In another, the difference between the new time interval and the pump stroke time duration is related to an amount of back pressure acting on the electrokinetic pump. In one embodiment, the pump stroke time duration is between about 300 milliseconds and about 500 milliseconds. In another aspect, the pump stroke time duration is between about 800 milliseconds and about 1 second. In another aspect, the output of the electrokinetic pump is provided against a backpressure of between about 3 psi—about 5 psi. In still another aspect, the method of controlling the output of an electrokinetic pump has a pump stroke time duration is more than 0 milliseconds and less than 500 milliseconds or the new time interval is zero or less than one second.

In still another alternative embodiment, there is a method of controlling the output of an electrokinetic pump under the control of a computer controller to deliver a target stroke volume. This method includes computer readable instructions for the performance of a number of different processing steps. The processing steps may include for example, applying a voltage to the electrokinetic pump for a pump stroke time duration; determining a volume of a delivery fluid pumped during the pump stroke time duration using an input from a differential pressure flow meter; comparing the volume of the delivery fluid pumped during the pump stroke time duration to the target stroke volume; generating a stroke time duration adjustment based upon the comparing step; applying a voltage to the electrokinetic pump in relation to the pump stroke time duration and the stroke time duration adjustment and others depending upon the particular configuration of the pumping system used. In one aspect, the voltage used in both applying a voltage steps is equal. The method may include determining a volume of a delivery fluid by measuring flow rates of a fluid flowing fluid through a differential pressure flow meter having a venturi flow meter, an orifice flow meter and/or a flow nozzle flow meter.

In one aspect, the step of determining a volume of a delivery fluid relies in part on a pressure sensor reading at the outlet to a flow restrictor downstream of the delivery chamber of the electrokinetic pump. In one embodiment, the step of determining a volume of a delivery fluid may use a pressure sensor reading at the outlet to a check valve downstream of the delivery chamber of the electrokinetic pump. In another aspect, the method of generating a stroke time duration adjustment is based upon a proportional feedback control scheme programmed into an electronic memory of the computer controller; a proportional and integral feedback control scheme programmed into an electronic memory of the computer controller; a proportional, integral and derivative feedback control scheme programmed into an electronic memory of the computer controller, each alone or in any combination.

In still another aspect, the comparing step includes a reading of a delivery fluid temperature. In one embodiment, the stroke time duration adjustment is based on the reading of a delivery fluid temperature or on a temperature compensation related to a delivery fluid temperature.

In another aspect, the steps of the method are repeated until a total volume delivery counter in the computer controller is incremented to the total volume delivery. Alternatively, the steps of the method are repeated until a total volume delivery counter in the computer controller is decremented to zero from a total volume delivery. Performance of the method steps may produce an output of about 3 microliters per stroke or about 0.5 microliters per stroke. Still further, the method is conducted where the delivery fluid pumped is a pharmacological agent and the steps of the method are repeated until a desired volume of is delivered. In the method, the desired volume is controlled by a value set in the computer controller to limit delivery of the pharmacological agent. In one aspect, the pharmacological agent is glucose. In still further aspect, the steps of the method are repeated to produce an output of the delivery fluid at a rate of about 0.09 ml/hour, or a rate of about 0.03 ml/minute. In one embodiment, the stroke time duration adjustment is completely applied to the immediate next pump stroke.

In still another aspect there is a method of controlling an output of an electrokinetic pump under the control of a computer controller having computer readable instructions to deliver a target stroke volume. The instructions include applying a voltage to the electrokinetic pump for a pump stroke time duration. In addition, there are instructions for processing a pressure signal related to the output of the electrokinetic pump; determining a volume of a delivery fluid pumped during the pump stroke time duration based at least in part on the result of the processing step; comparing the volume the delivery fluid pumped during the pump stroke time duration to the target stroke volume; generating a stroke time duration adjustment based upon the comparing step; and applying a voltage to the electrokinetic pump in relation to the pump stroke time duration and the stroke time duration adjustment.

While executing these instructions, the pressure signal related to the output of the electrokinetic pump is provided by a pressure sensor in direct communication with the electrokinetic pump outlet. Alternatively, the pressure signal related to the output of the electrokinetic pump is provided by a pressure sensor measuring a pressure reading influenced by the operation of a check valve. Alternatively, the pressure signal related to the output of the electrokinetic pump is provided by a pressure sensor measuring a pressure reading related to a component in a differential pressure flow meter. In another aspect, instructions used for performing the method include generating a stroke time duration adjustment that is based upon a proportional feedback control scheme; a proportional and integral feedback control scheme; or a proportional, integral and derivative feedback control scheme. In still another aspect, the instructions for the method related to the stroke time duration adjustment are used to select a duration from one of a plurality of pre-programmed stroke time durations closest to the result of the comparing step.

In another alternative embodiment of an electrokinetic pump fluid delivery system, there is a system having an electrokinetic pump in communication with an outlet chamber, a reservoir in communication with the outlet chamber; and a differential pressure flow control system in communication with the outlet chamber. There is provided in accordance with the disclosure above a control system for the delivery system implemented using an electronic controller. The controller is in communication with the electrokinetic pump and the differential pressure flow control system as suited to the specific components thereof. The instructions in the memory of the controller may also include those adapted and configured for communication to and from a differential pressure control system. Such communication includes instructions for the specific components of a differential pressure system including power, control, instructions, data, or other signaling turning components on or off, calibration of said components. Examples of specific components may include those associated with a venturi flow meter, an orifice flow meter, or a flow nozzle flow meter.

The memory of the controller or suitable memory in communication with or accessible to the controller contains computer readable instructions to determine or retrieve data relating to, for example, a pump drive signal, a constant voltage value, a constant current value, a pump stroke time based a correction factor. In one aspect, there is a time based correction factor is based upon a value in a look up table programmed into or accessible to an electronic memory of the computer controller. Still further, a correction factor may be related to a number of different variables or system conditions as described above. The correction factor may be, for example, provided or determined in relation to an input signal to the controller from the electrokinetic pump and an input signal to the controller from the differential pressure flow control system. As such, the electronic memory accessible to the controller may include or be programmed to include, for example, a time based correction factor is based upon a feedback control scheme. Additionally or alternatively, the electronic memory of the computer controller is programmed for or has access separately or in any combination to: (a) a proportional feedback control scheme; (b) a proportional and integral feedback control scheme; and (c) a proportional, integral and derivative feedback control scheme.

Those of ordinary skill will appreciate that the various processing steps, comparisons, methods, techniques, signal processing and component specific operations performed by a controller are provided to the controller or contained within electronic memory accessible to the controller in the form of appropriate computer readable code. Similarly, the various diagnostic routines, abnormal condition detectors, functional indicators and pump control schemes and other operational considerations described in this patent application are also stored in an appropriate computer readable code within the memory of or accessible to the controller. In one specific example, the computer readable instructions in the memory of the computer controller implement control schemes for pump cycle duration based on computations made based at least in part on a differential pressure flow control (instructions to adjust the pump duration based on a calculated stroke time adjustment), including techniques described herein for stroke duration response is calculated, as well as the tables, files or data relating to those embodiments where the stroke response adjustment is selected one of a set of pre-selected stroke durations.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity in the claims that follow. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which.

In the drawings:

FIG. 1 is a schematic view of an embodiment of a differential pressure control system at the outlet of an electrokinetic pump having two pressure sensors and a flow restrictor between two system check valves;

FIG. 2 is a section view of an embodiment of an electrokinetic pump block that incorporates differential pressure control system components described in FIG. 1;

FIG. 3A is an exemplary method of controlling an electrokinetic pump using a pump drive signal on duration in a differential pressure control scheme;

FIG. 3B is an exemplary method of controlling an electrokinetic pump using voltage on duration in a differential pressure control scheme;

FIG. 4 is an exemplary graph of sensor output in millivolts versus time in milliseconds for the output of the pressure sensors PS1 and PS2 (see FIGS. 1 and 2);

FIG. 5 is an exemplary correlation curve for the differential pressure control system described in FIG. 1;

FIGS. 6A, 6B and 6C illustrate alternative differential pressure control schemes that employ a single pressure sensor and a single flow restrictor;

FIG. 7 is a performance graph of an electrokinetic pump system arranged as in FIG. 6A showing average stroke volume in microliters (μl) versus differential pressure integral values for backpressure conditions of 0, 1.7 and 2.7 psi;

FIG. 8 is a performance graph of an electrokinetic pump system arranged as in FIG. 6A for delivery flow rate of 8 mL/hour using a target stroke of 20 mL in a differential pressure control method under back pressure conditions of 0 psi, about 2.3 psi, and about 4.2 psi;

FIG. 9A is a schematic view of an electrokinetic pump using a differential pressure control system where a system component (i.e., a check valve) is used as the flow restrictor between the pressure sensors PS1 and PS2; FIG. 9B is a schematic view similar to FIG. 9B with a flow restrictor downstream of PS2;

FIG. 10 is a section view of an embodiment of an electrokinetic pump block that incorporates differential pressure control system components described in FIG. 9A;

FIG. 11 is a schematic view of an embodiment of a differential pressure control system as in FIG. 1 with a temperature sensor added to measure incoming fluid temperature for viscosity correction;

FIGS. 12 and 13 illustrate, respectively, pump output curves for using differential pressure controls without and with temperature compensation for viscosity correction.

FIG. 14 is an electrokinetic pump pressure response curve for a single pressure sensor output showing an adjustment in voltage duration between successive pump strokes;

FIG. 15 is an electrokinetic pump pressure response curve for a two pressure sensor output showing an adjustment in voltage duration between successive pump strokes;

FIG. 16 is a table showing exemplary values of electrokinetic pump correction time as related to pump stroke time;

FIG. 17 is a table showing exemplary correction values and corresponding correction times for one illustrative electrokinetic pump control scheme;

FIG. 18 is an exploded view of a control module; and

FIG. 19 is a schematic diagram of the electrical connections between components of a pump module and components of a control module.

DETAILED DESCRIPTION

In one aspect of the present invention, differential pressure control techniques are used to monitor and control the output and performance of an electrokinetic pump (EK pump). In general, readings from pressure sensors at different locations in the pump system collect pressure information in relation to pump stroke. This information is then used to determine flow rate. Pressure curves may be integrated to obtain a flow volume. This information and technique permits a determination of the amount of delivery fluid delivered by the pump system. In one aspect of a control system, subsequent EK pump strokes can be adjusted such as by lengthening or shortening the pump duty cycle. In terms of an EK pump, one can lengthen or shorten the duty time by varying the time which voltage is applied to the pump element in order to adjust the flow volume.

The methods and systems described herein are designed to take advantage of the unique operating characteristics of the electrokinetic pump. Chief among these characteristics is the highly responsive nature of EK pumps to a drive signal. The application of the drive signal leads nearly simultaneously to movement of fluid from the pump and with that movement useful work may be performed by the system. A variety of EK system configurations and differential pressure control schemes are described herein. Each of these systems take advantage of the controllable nature of each EK pump stroke that permit the use of partial strokes or strokes that are less than full pump stroke. As a result, by using the flow control feedback of each stroke, any variation in stroke performance may be compensated in the subsequent stroke. Stroke by stroke error compensation as described herein provides highly precise flow control. In some embodiments, the correction of the pump stroke is made in the form of adjusting the length of time the pump control signal is applied to the EK pump. The magnitude of a correction value for pump on duration may be determined using any of a number of techniques. One technique is to calculate volume at the end of the stroke and then compare to a target stroke volume. Another technique is to calculate the stroke during delivery volume as it occurs until the target stroke delivery volume is reached. Still another technique is to read the parameters of the pump output (for example, back pressure) and then estimate, calculate or look up from a table a likely pump stroke duration to deliver a desired volume at that pump output condition.

A reciprocating pumping system driven by electrokinetic engine (EK engine or EK pump) uses a pressure sensor feedback scheme to control the amount of fluid delivered. An EK engine includes a silica porous membrane, two porous electrodes, a housing, a rear diaphragm, and a front diaphragm. The EK pump is used to drive a reciprocating pump. A number of alternative reciprocating pump configurations are described below. Typically the reciprocating pump includes a reservoir, check valves, pressure sensors, and some type of a flow restrictor. As will be described in greater detail below, the working fluid, buffer, and the delivery fluid (i.e., a pharmacologically active material or drug) is separated by the front diaphragm. In a different arrangement, a gel coupling is used in place of the front diaphragm. The gel coupling is further described in co-pending and commonly owned U.S. Provisional Patent Application No. 61/482,889, entitled “GEL COUPLING FOR ELECTROKINETIC DELIVERY SYSTEMS” filed May 5, 2011 and its corresponding U.S. Non-provisional patent application Ser. No. ______, entitled “GEL COUPLING FOR ELECTROKINETIC DELIVERY SYSTEMS,” filed herewith, each of which are incorporated herein by reference in its entirety.

An electronic controller, along with supporting electronic elements, controls the pump drive signal supplied to the EK engine, the direction of the current through the EK engine, as well as receiving and measuring the pressure signals generate by the pressure sensors. In one aspect, the pump drive signal is a voltage. The electronic controller may be a microcontroller, microprocessor or other suitable pump controller. In another aspect, the pump drive signal is a current. In one aspect, the pump drive signal maintains a constant amplitude during a pump stroke. In another aspect, the pump drive signal has one constant amplitude during one stroke and then a different pump drive signal amplitude in a subsequent stroke. One example of different pump signal amplitudes may be appreciated with reference to a voltage drive signal. In one stroke a 3 v signal may be used. In a subsequent stroke as a result of an indication of back pressure for example, a voltage of 6 volts may be used. Thereafter, when the back pressure condition has cleared the system may return to the 3 v drive signal. As such, in one aspect of the control system, amplitude of a pump drive signal may be selected and then the duration of the application of that pump drive signal controlled and compensated using the differential pressure techniques described herein.

The EK engine generates hydrostatic pressure by expanding or contracting the front diaphragm. Front diaphragm expansion is achieved by applying a constant forward voltage from rear electrode to front electrode. Current thus flows through the silica and generates buffer fluid movement from the rear diaphragm to the front diaphragm. The front diaphragm collapses by applying a reverse voltage, from front electrode to the rear electrode. Current thus flows through the silica and generates buffer fluid movement from the front to the rear.

Movement of the delivery fluid is generated by the movement of the front diaphragm. A negative hydro static pressure is generated when the front diaphragm is moved (collapsed) toward the EK element and expands the volume in the chamber. This negative pressure (pressure below atmospheric) withdraws fluid from the reservoir, through the inlet check valve, and into the chamber. The outlet check valve prevents the fluid on the outlet side from coming back into the chamber. A positive hydro static pressure is generated as the front diaphragm is moved (expands) away from the EK element and collapses the volume in the chamber. This positive pressure (pressure above atmospheric) pushes fluid from the chamber, through the outlet check valve, and into the delivery point. The inlet check valve prevents the fluid in the chamber from going back into the reservoir.

The amount of delivery fluid being delivered is directly proportional to the amount of EK buffer being moved. In turn, the EK buffer moved is directly proportional to the current used. The delivery fluid can be controlled very precisely using the pressure sensors as a feedback control. In the different arrangements set forth below, the pressure sensor or sensors are used to calculate the delivered volume. Once the delivered volume is determined, the duration of the time period which the constant forward voltage is supplied, thus the forward current, is lengthened or shortened as needed. If the calculated volume is high, the next delivery's period is shortened. Likewise, if the calculated volume is too low, the delivery period is lengthened. These adjustments are made until the desired volume is delivered within prescribed tolerances. The variations in stroke duration provide a broad range of partial stroke delivery schemes. In the context of these various embodiments, a partial stroke is a stroke of a duration that leads to deflection of the front diaphragm into the delivery chamber that does not completely empty the delivery fluid in the delivery chamber. In contrast, a full stroke would be a pump stroke duration that would deflect the front diaphragm sufficiently into the delivery chamber such that all or substantially all of the delivery fluid in the delivery chamber is pumped out. The ability of the system configurations and methods described herein to provide partial strokes leads to greater flexibility in both delivery as well as error correction.

To prevent hydrolysis of the pump working fluid, the EK pump is operated with a drive voltage that provides controllable flow without hydrolysis and resultant gas generation. The charge balance on the electrodes is maintained such that the exact amount of charge (current) is charged and then discharged during each EK pump cycle. The most common technique for this balance is to select drive currents below the hydrolysis limit and then employ equal duration reverse and forward drive currents. These and other details of electrokinetic pump design and operation are described in commonly owned U.S. Pat. No. 7,235,164, incorporated herein by reference in its entirety.

The reciprocating pump by nature is not a continuous pump. Each pump cycle has a intake stroke and a delivery stroke. There are inactive periods between each successive stroke. We define the dwell period as the time between the intake and the delivery stroke, and the wait period as the time between the delivery stroke and the intake stroke. The pump operates as wait time, intake stroke, dwell time, and delivery stroke. To adjust flow rate, we fix the stroke volume and adjust the wait time: for faster flow rates the wait time is short; and slower flow rates, the wait time is long. In one alternative embodiment, an additional wait time or delay may be used to permit synchronization with one of more EK pumps when multiple pumps are employed. The control techniques described herein may be used to control each pump in a multiple pump configuration as described, for example, in co-pending and commonly assigned U.S. Provisional Patent Application No. 61/482,949, entitled “GANGING ELECTROKINETIC PUMPS,” filed May 5, 2011 and its corresponding U.S. Non-provisional patent application Ser. No. ______, entitled “GANGING ELECTROKINETIC PUMPS,” filed herewith, each of which are incorporated herein by reference in its entirety.

The incorporation of differential pressure control techniques and information and appropriate correlation curves provides greater control the amount of fluid being delivered by the EK pump. There are several alternative methods of using this information for pump control. Feedback control may include one or more of: (a) proportional feedback control; (b) proportional and integral feedback control; or (c) proportional, integral and derivative feedback control separately or in any combination.

One method used is the direct control of the EK pump. Using this method, the drive current or voltage is applied until the target volume is delivered. The system pressure sensors are sampled during the application of the drive voltage, integrated and used to determine volume delivered. Once the targeted delivery volume is reached, the drive voltage is shut off and the EK pump flow stops. Put simply, a drive current or voltage is applied to the EK pump until the integral value reaches the desired or targeted value.

Alternatively, the EK pump delivery operation could be operated for an approximated time selected to deliver a targeted stroke volume. During each EK pump cycle, the pressure sensors are sampled and used to generate a pressure curve. The pressure curve integration yields the actual fluid delivered during the stroke. Comparison of the estimated and actual stroke volumes may then be used to find the appropriate response to adjust the EK pump delivery operation. Control responses for the EK pump include one or more of adjusting drive current, drive voltage or time of drive stroke, and combinations thereof.

In a system utilizing a constant drive current or voltage, the control response may include adjusting the time duration of each pump stroke. This control response may be accomplished in a number of ways. One way is to use a look up table. Under this control scheme, a look up table of pre-generated pump stroke volumes is used for comparison to the measured stroke volume. Based on the result of that comparison, the time duration of the next stroke is adjusted longer or shorter based on the result. If actual stroke delivery was lower than predicted, the pump time is increased. If actual stroke delivery was higher than predicted, the pump on time is decreased. In this method, first estimate a time to power the EK pump for a targeted stroke delivery target and then run the EK pump for this estimated time. Sample the pressure sensors during this time and calculate an integral value for actual volume delivered. Thereafter, compare the actual and estimate volumes and adjust the next stroke time as needed.

In another control method, a function is used to determine the appropriate response. The function may be a first or higher order equation used to determine how and to what degree subsequent pump strokes are adjusted.

Using information about comparison between projected/estimated and actual pump delivery, the system may estimate the time duration for the next pulse sent to the pump. FIG. 12 illustrates the accuracy of the pump using this control scheme. The pump is pumping 20 μl per stroke within +/−5% over a 24 hour period. This degree of stability has been demonstrated for stroke volumes as small at 0.5 μl. The high degree of control is also illustrated by the fine level of per stroke correction. FIG. 16 relates the per stroke correction amounts to some exemplary flow rates.

FIG. 1 is a schematic view of an embodiment of an EK pump used to deliver fluid using an exemplary differential pressure control system. The outlet of the EK pump is provided to a pump chamber between two system check valves. There are two pressure sensors and a flow restrictor between the two system check valves. The pressure sensors and the flow restrictor are arranged to provide a differential pressure flow meter. The system also includes a reservoir containing a fluid to be delivered by action of the electrokinetic pump. The electrokinetic pump is connected to an outlet chamber. An inlet check valve separates the outlet chamber from the reservoir and the outlet check valve separates the pump components from the delivery site or outlet.

FIG. 1 also illustrates a power source 180 and a controller 175 used to operate the EK pump. The controller 175 functions based on the pump control scheme selected, inputs from the pressure sensors 152, 154 and desired pump stroke volume or target volume. The controller 175 includes memory with computer readable instructions to implement the pump control scheme including for example receiving and interpreting signals from system components such as the pressure sensors, perform calculations according to the control scheme and providing control signals to the EK pump. The controller can be a microcontroller with sufficient inputs and outputs depending upon the number of systems components used in a particular configuration (number of pressure sensors, elements of a differential pressure system, for example). One commercially available microcontroller suited to the configurations described herein is the C8501F310, available from Silicon Laboratories Inc., Austin, Tex. In another alternative, the microprocessor or the computer used as a controller includes a minimum of 4 A-D converters and 16 digital IOs. Additional details of other suitable controller types are described below with regard to FIGS. 18 and 19.

FIG. 1 illustrates a typical differential pressure flow control arrangement with a pair of pressure sensors 152, 154 on either side of a flow restrictor 160. In the illustrated schematic, the pair of pressure sensors PS1 (152) and PS2 (154) are placed on either side of a flow restrictor 160. The pressure sensors may be any suitable pressure sensor suited to the range of pressures and flows used in the system. The system illustrated in FIG. 1 is typically used for flow applications in the range of 0.01 ml/hr to 50.0 ml/hr at pressures ranging from 0 to 6 psi. In one specific embodiment, the pressure sensors are commercially available from Measurement Specialties of Fremont, Calif.

The flow restrictor 160 may be any suitable flow restrictor according to the type of measurement scheme being used. For example, the flow restrictor may be configured as a venturi, an orifice, a flow nozzle or any other suitable configuration. The flow restrictor along with one or more pressure sensors may be arranged for operation as a differential pressure flow meter. Exemplary differential flow meter configurations include: a Venturi flow meter, an orifice flow meter or a flow nozzle flow meter.

The advantage is that most external noise (i.e., outside of the pump system) is isolated by the outlet check valve 144. In this configuration, the calculations used to determine pump rate are simpler because the pressure curve from each pressure sensor is subjected to any variations caused by the outlet check valve 144. Since this variable is included in both pressure sensor readings, the control value of interested is obtained using the difference between the two pressure curves shown below in FIG. 4 and expressed as:

∫((PS2(t)−PS1(t)))dt*Constant (so called difference area under the curve or the difference integral)

Using this scheme produces a good correlation between flow volume and the difference integral value.

FIG. 2 is a section view of an embodiment of an electrokinetic pump block that incorporates differential pressure control system components described in FIG. 1. The internal components and arrangement of the EK pump are visible in this view. In this configuration, the EK engine 103 operates to move front and rear EK diaphragms placed on either side of the EK engine. The EK pump diaphragms deflect in response to the movement of the working or pump fluid as drive current is applied to the EK pump. Additional details of the operation of EK pumps, diaphragms and pump system configurations are available in commonly owned, co-pending U.S. patent application Ser. No. 12/327,568 published as U.S. Patent Application Publication US 2009/0148308 entitled “Electrokinetic Pump With Fixed Stroke Volume,” the entirety of which is incorporated herein by reference.

Referring to FIG. 2, an electrokinetic (“EK”) pump assembly 100 includes an EK pump 101 connected to an EK engine 103. The EK engine 103 includes a first chamber 102 and a second chamber 104 separated by a porous dielectric material 106, which provides a fluidic path between the first chamber 102 and the second chamber 104. Capacitive electrodes 108 a and 108 b are disposed within the first and second chambers 102, 104, respectively, and are situated adjacent to or near each side of the porous dielectric material 106. The EK engine 103 includes a movable member 110 in the first chamber 102, opposite the electrode 108 a. The moveable member 110 can be, for example, a flexible impermeable diaphragm. A pump fluid (or “engine fluid”), such as an electrolyte, can fill the EK engine, such as be present in the first and/or second chambers 102 and 104, including the space between the porous dielectric material 106 and the capacitive electrodes 108 a and 108 b. The capacitive electrodes 108 a and 108 b are in communication with an external voltage source, such as through lead wires or other conductive media.

The EK pump 101 includes a delivery chamber 122 and a movable member 113 having a first edge 112 contacting the delivery chamber 122 and a second edge 111 contacting the second chamber 104. In some embodiments, the first and second edges 112, 111 are flexible diaphragms having a mechanical piston therebetween. In other embodiments, the first and second edges 112, 111 are flexible diaphragms having a gel material therebetween. Gel couplings are described further in U.S. Provisional Patent Application No. 61/482,889, filed May 5, 2011, and entitled “GEL COUPLING FOR ELECTROKINETIC DELIVERY SYSTEMS,” and U.S. patent application Ser. No. ______, filed herewith, and entitled “GEL COUPLING FOR ELECTROKINETIC DELIVERY SYSTEMS,” the contents of both of which are incorporated herein by reference. In other embodiments, the first and second edges 112, 111 are edges of a single flexible member or diaphragm.

The delivery chamber 122 can include a delivery fluid, such as a drug or medication, e.g., insulin or pain management medications, or a cleansing fluid, such as a wound cleansing fluid, supplied to the delivery chamber 122 from a fluid reservoir 141. An inlet check valve 142 between the fluid reservoir 142 and delivery chamber 122 can control the supply of delivery fluid to the delivery chamber 122, while an outlet check valve 144 can control the delivery of delivery fluid from the delivery chamber 122, such as to a patient. A first pressure sensor 152 and a second pressure sensor 154 can monitor the flow of fluid from the system. Further, a flow restrictor 160 can be present in the pump 101 to produce a pressure differential between sensors 152, 154 so as to provide a mechanism for measuring the flow of the fluid.

In use, the electrokinetic assembly 100 works by producing electrokinetic or electroostmostic flow. A voltage, such as a positive voltage, is applied to the electrodes 108 a, 108 b, which causes the engine fluid to move from the second chamber 104 to the first chamber 102. The engine fluid may flow through or around the electrodes 108 a and 108 b when moving between the chambers 104, 102. The flow of fluid causes the movable member 110 to be pushed out of the chamber 102 and the movable member 113 to be pulled into chamber 104. As a result of the movement of the movable member 113, delivery fluid is pulled from the reservoir 141 into the delivery chamber 122. The movement of delivery fluid from the reservoir into the delivery chamber 122 is called the “intake stroke” of the pump cycle. When the opposite voltage is applied, such as a negative voltage, fluid moves from the first chamber 102 to the second chamber 104. The movement of engine fluid between chambers causes the movable member 110 to be pulled into the first chamber 102 and the movable member 113 to expand to compensate for the additional volume of engine fluid in the second chamber 104. As a result, delivery fluid in the chamber 122 is pushed out of the chamber 122 and delivered, such as to a patient, through the outlet check valve 144. The delivery of fluid is called the “outtake stroke” of the pump cycle. Although the exemplary assemblies and systems described below are configured such that a positive voltage corresponds to the intake stroke and a negative voltage corresponds to an outtake stroke, it is to be understood that the opposite configuration is also possible—i.e., that a negative voltage corresponds to an intake stroke and a positive voltage corresponds to an outtake stroke.

FIGS. 3A and 3B describe exemplary methods of controlling the operation of an electrokinetic pump system using a differential pressure flow measurement technique.

FIG. 3A is an exemplary method 200 of controlling an electrokinetic pump using pump drive signal on duration in a differential pressure control scheme. This method determines a pump drive signal on duration when the pump drive signal amplitude is maintained constant. A variety of pump drive signals may be used such as voltage, current or electrode charge, for example.

First at step 205, the pump drive signal is applied to an electrokinetic pump for a time duration. The time duration used is based on a number of factors such as prior pump performance, calibration curves or experimental information. The time duration is selected to produce or deliver a target stroke volume which is a partial stroke of a full stroke.

Next, at step 210, a differential pressure technique is used to determine the stroke volume during the time duration selected in step 205. The result of this process is the determined stroke volume.

Next at step 215 the determined stroke volume is compared to the target stroke volume. Next, at step 222, evaluate whether or not the total volume has been delivered. This step looks to the determination of whether the volume calculated in step 210 actually completed delivery of a total volume. The total volume delivery could be maintained by any number of techniques. In one aspect, the total volume delivery is a counter that decrements from a total volume amount. In another aspect, the total volume delivery is a counter that increments from zero to the desired total volume amount. As a result, the step of incrementing or decrementing the total volume may be performed once the volume of that last stroke is determined. Thereafter, the decision proceeds based on whether the total volume was delivered. If YES, then the controller generates a stop pump command (step 224). In addition, the system may generate an output or indication that the total volume is delivered. If the answer in step 222 is NO, the after the counter is indexed, the method then proceeds.

Next, evaluate whether or not the target stroke volume has been delivered (step 220). If the target stroke volume has been delivered and the answer is YES then no correction is needed (step 225) and the next pump stroke will apply the drive voltage for the same duration (i.e., returning to step 205 until the total volume is delivered).

If however the target stroke volume was not delivered (answer at block 220 is “no”), then proceed to step 230. In this step a pump on duration is generated based on the comparison of determined stroke volume and target stroke volume. The pump duration adjustment can be positive i.e., an increased duration if the determined stroke volume is smaller than the target stroke volume. Conversely, the pump duration adjustment can be negative i.e., a decreased duration if the determined stroke volume is greater than the target stroke volume.

Depending on the result of step 230, the pump drive signal on duration is then applied to the EK pump on the next pump stroke (step 235). Thereafter, the process repeats at the determining step 210 to determine the volume of delivery fluid delivered during step 235.

FIG. 3B is an exemplary method 300 of controlling an electrokinetic pump using voltage on duration in a differential pressure control scheme. This method determines the voltage on duration when drive voltage is maintained constant.

First at step 305, the drive voltage is applied to an electrokinetic pump for a time duration. The time duration used is based on a number of factors such as prior pump performance, calibration curves or experimental information. The time duration is selected to produce a deliver a target stroke volume which is a partial volume of a full stroke volume

Next, at step 310, a differential pressure technique is used to determine the stroke volume during the time duration selected in step 305. The result of this process is the determined stroke volume.

Next at step 315 the determined stroke volume is compared to the target stroke volume. Next, at step 322, evaluate whether or not the total volume has been delivered. This step looks to the determination of whether the volume calculated in step 310 actually completed delivery of a total volume. The total volume delivery could be maintained by any number of techniques. In one aspect, the total volume delivery is a counter that decrements from a total volume amount. In another aspect, the total volume delivery is a counter that increments from zero to the desired total volume amount. As a result, the step of incrementing or decrementing the total volume may be performed once the volume of that last stroke is determined. Thereafter, the decision proceeds based on whether the total volume was delivered. If YES, then the controller generates a stop pump command (step 324). In addition, the system may generate an output or indication that the total volume is delivered. If the answer in step 322 is NO, the after the counter is indexed, the method then proceeds.

Next, evaluate whether or not the target stroke volume has been delivered (step 320). If the target stroke volume has been delivered and the answer is YES then no correction is needed (step 325) and the next pump stroke will apply the drive voltage for the same duration (i.e., returning to step 305).

If however the target stroke volume was not delivered (answer at block 320 is “no”), then proceed to step 330. In this step an additional pump on duration is generated based on the comparison of determined stroke volume and target stroke volume. The pump duration adjustment can be positive i.e., an increased duration if the determined stroke volume is smaller than the target stroke volume. Conversely, the pump duration adjustment can be negative i.e., a decreased duration if the determined stroke volume is greater than the target stroke volume.

Depending on the result of step 330, the pump drive signal on duration is then applied to the EK pump on the next pump stroke (step 335). Thereafter, the process repeats at the determining step 310 to determine the volume of delivery fluid delivered during step 335.

As a result of the use of the total volume counter, the EK pumping system may be used to determine an estimated number of strokes to deliver a remaining total volume. Consider for example a pump operations scenario where the operating conditions have resulted in a lower than expected delivery fluid pumped by the system. In this instance, the total volume counter will have some amount of undelivered total volume. The system controller may also include computer readable instructions to calculate an estimated number of additional delivery strokes needed to pump the balance of the total delivery volume. Thereafter, the controller would continue to operate the cycle pump strokes until the total volume is delivered.

FIG. 4 is an exemplary graph of sensor output in millivolts (mV) versus time in milliseconds for the output of the pressure sensors PS1 and PS2 (see FIGS. 1 and 2) during a pump stroke. In this configuration 500 mV equates to a 0 psi reading. Voltage is applied to the pump at about 8000 ms as the trace crosses the 500 mV line. Next at about 9700 ms and 800 mV, the outlet check valve cracks and flow begins. After this point, the readings from PS1 and PS2 separate. The upper solid line comes from PS1 and the lower dashed line comes from PS2. The drive voltage is turned off at time 10,000 ms where PS1 reads about 890 mV. Shortly thereafter at approximately 10,500 ms at about 840 mV the curves for PS1 and PS2 converge back into a single trace. The controller evaluates the readings from PS1 and PS2 to obtain the area between the PS1 and PS2 curves while they are separated. The area between these curves then used to control subsequent pump strokes using one or more of the control schemes described herein. The gradual decrease in the PS1/PS2 curve is related to the gradual system pressure decrease between pump strokes.

FIG. 5 is an exemplary correlation curve generated and used for a differential pressure control system described in FIGS. 1 and 2. The x axis is the DPI (differential pressure integral) value and the Y axis is the measure mass delivered during the flow that generated the DPI. The curve shown has a good linear fit as illustrated by the solid series 1 fit line. From such a correlation curve, a delivered mass or volume can be calculated from the DPI values observed during pumping system operation.

FIG. 6A illustrates an alternative differential pressure control scheme. FIG. 6A is similar to FIGS. 1 and 2 in many respects. The main difference between the system on FIG. 6A and the earlier described systems is that this system relies on a single pressure sensor (PS2). There is also a flow restrictor 160 between the outlet chamber 122 and the pressure sensor 154 (PS2). In another optional configuration, a single flow restrictor 160 is positioned between PS2 and the outlet check valve 144 (see FIG. 6B). In this configuration, there is an assumed constant back pressure on the flow restrictor. The controller scheme used in this type of system is different since it relies on an assumed constant back pressure to eliminate the need of a second pressure sensor. Control of an EK pump in this configuration is simplified as a result. In still another optional configuration, the flow restrictor 160 is positioned after the outlet check valve 144 (see FIG. 6C). Moreover, the electronic memory, routines and computer readable instructions performed by the controller 175 will be different and based on performance parameters and curves from a single pressure reading configuration as well as the specific component configuration selected (e.g., FIG. 6A, 6B or 6C).

This so called single pressure sensor method uses a single pressure sensor to determine pump flow. Assuming that during “off pump” periods the pump is not delivering any fluid, then during this time, PS2 is measuring the back pressure applied to the system. This control scheme assumes as well that the back pressure does not change during delivery time. For example, for a pump designed to deliver 0.5 μl to 3 μl per stroke, typically less than one and half second, for 0.5 μl partial stroke with a 5 psi back pressure it is in the range from about 0.65 to 1.5 sec., or for 0.5 μl partial stroke with no back pressure it is 0.30 to 1.5 sec. or in any of the ranges of FIG. 16. As such, when the pump is powered on, the pump stroke flow rate is equal to the difference the increase in pressure and the initial pressure. This operation can be expressed as:

∫(PS2(t)−PS2(t0))dt*Constant (so called area under the curve or the integral)

Whereas the constant is associated with one or more of the properties of the fluid such as viscosity, density, and/or friction. One or more of these properties may change depending upon variations in, for example, the operating temperature of the pump, temperature of the delivery fluid, or environmental conditions such as temperature surrounding the reservoir or delivery site.

To use this scheme, first generate a correlation curve for each particular system and anticipated stroke length. Here stroke length refers the length of time that a specific drive signal is applied to an EK pump. This graph is used to produce the correlation between the “integral” values and the actual amount for fluid delivered. The correlation values are generated by operating the EK pump within the expected performance area during a present cycle time. The EK pump will be run for a preset number of cycles with a preset stroke length. The stroke duration (i.e., pump on signal time or duration of pump drive signal) will be kept constant for all strokes. The EK pump outlet is configured for delivery to a scale thereby permitting the mass of fluid delivered to be measured. Using the appropriate density value for the delivery fluid, the delivery volume is calculated and then divided into the number of strokes to yield the per stroke volume for that pump stroke. The procedure is repeated for two, three, four or more different pump stroke lengths or pump on or pump drive signal durations. The correlation curve for that pump is produced by plotting the results of these various stroke length tests and applying a suitable curve fit technique. The appropriate correlation curve is loaded into the controller to control stroke volume during pump operations. After obtaining the various correlation values, we then measure this measured pump performance against a number of exemplary back pressure values to ensure the accuracy of the correlation curve. A typical graph of one such test is shown below in FIG. 7. Note that the pump performance against a variety of back pressures is very linear.

FIG. 7 is a performance graph of an electrokinetic pump system arranged as in FIG. 6A showing average stroke volume in microliters versus differential pressure integral values for backpressure conditions of 0, 1.7 and 2.7 psi. The correlation values in this graph would be used to adjust pump performance as delivery circumstances change.

Additional experiments reveal that the pressure differential control schemes described herein produce integral values that are back pressure independent up to back pressures as high as 6 psi. The pumping systems and control schemes described herein are capable of fully compensating for the likely range of back pressures encountered during delivery to mammals.

FIG. 8 is a performance graph of an electrokinetic pump system arranged as in FIG. 6A for delivery flow rate of 8 mL/hour using a target stroke of 20 μl in a differential pressure control method as described herein. The typical duty cycle parameters are 3 volts for 600 ms. The duty cycle may range from 500 ms to about 1 sec. In the example control response illustrated in FIG. 8 the pump duty cycle was changed using fixed time intervals of 5 ms, 10 ms, 25 ms and 50 ms according to required pump response. These additional pump on durations are added or subtracted from the basic pump duty cycle (see FIG. 3A steps 230, 235 and FIG. 3B steps 330 and 335). In this particular example, the control system is responding to three back pressure conditions: no back pressure or 0 psi, a back pressure of about 2.3 psi, and a back pressure of about 4.2 psi.

As can be seen from the graph during the 0 psi or no back pressure scenario from 0-600 seconds, the pump is consistently delivering the target stroke volume of 20 μl per stroke. At time 600 seconds, a back pressure of about 2 PSI is applied. Note that the next measured stroke volume immediately drops to about 17 μl. As the control algorithm takes over and pump stroke duration is adjusted as in FIGS. 3A and 3B, the stroke volume increases over a few cycles until the stroke target volume of 20 μl is reached. The pump on time is increased here to provide the added volume to overcome the impact of the back pressure.

At time 1000 seconds, the back pressure returns to zero. With the back pressure removed the stroke volume over delivers as shown with the spike to about 22 μl at time 1020 seconds. Thereafter, the controller shortens the pump on time in the successive strokes. By about time 1100 seconds, the controller has returned the stoke volume back down to the target stroke volume of 20 μl.

At time 1300 seconds, a back pressure of about 4 psi is applied to the system. Note the immediate drop in actual stroke volume to about 13 μl. The control algorithm then begins adjusting each subsequent stroke by increasing pump on duration until by about time 1500 seconds the actual stroke volume is back on target at 20 μl. At time 1700 seconds another excursion in pump stroke volume is observed as the 4 psi back pressure is removed. As before with the 2 psi back pressure, the control system adjusts (i.e., decreases) the duration of the voltage on during the pump stroke. As before, the control system quickly returns the actual pump stroke volume to the target pump stroke volume of 20 μl by about time 1800 seconds.

In FIG. 8 each point on the graph is a stroke volume reading. As described above, once a back pressure is applied to the system, the stroke volume drops. In this exemplary configuration, the control system feedback will adjust the stroke volume to the set level after a back pressure is applied or removed without about 7 pump strokes.

FIG. 9A is a schematic view of another alternative electrokinetic pump system configured for use with a differential pressure control scheme. In this configuration, the pump and components are similar to those previously described. In the embodiment of FIG. 9, a system component (i.e., a check valve 144) is used as the flow restrictor between the pressure sensors PS1 and PS2 (152, 154). Additionally or alternatively, a flow restrictor may also be placed between the outlet check valve and PS2 or beyond PS2 (see FIG. 9B).

FIG. 9A illustrates a pressure sensor (152/PS1) is located on the pumping chamber 122, and the second pressure sensor (154/PS2) is located after the outlet check valve 144. A flow restrictor 160, such as a 26 gage needle (for example), may be located in front of the pressure sensor (154/PS2) between PS2 and the outlet check valve 144 or downstream of the pressure sensor (see FIG. 9B). In this configuration a pressure difference method may be used to determine the volume produced during a pump stroke. This control scheme utilizes the difference between the pressure read at PS1 and PS2. In addition, this control scheme takes into account the check valve cracking pressure according to:

∫(PS1−Check valve cracking pressure−PS2)dt*Constant.

While described in this embodiment, check valve cracking pressure compensation may be applied to other control schemes described herein.

FIG. 10 is a section view of an embodiment of an electrokinetic pump block that incorporates differential pressure control system components as described in FIG. 9A.

FIG. 11 is a schematic view of an embodiment of a differential pressure control system as in FIG. 1 with a temperature sensor 185 added to measure incoming fluid temperature for viscosity correction.

Temperature Compensation for EK Pump Operation

Adding a temperature sensor to measure the surround temperature or the fluid temperature, we can compensate for more effects. Viscosity and density of a fluid changes with temperature. Also, there are some temperature affects on most pressure sensors. Thus adding a temperature sensor 185, as shown in FIG. 11, permits temperature measurements and compensation schemes based on temperature induced variations to the delivery fluid. The temperature sensor 185 is shown between the inlet check valve 142 and the pump chamber 122/PS1 152 location. The temperature sensor 185 could be located in any of a number of different locations along the fluid path shown in FIG. 11.

It is believed that the use of a temperature sensor permits pump stroke volume to be adjusted in order to compensate for delivery liquid viscosity. The result of compensation may well be within +/−2% as shown in the following figures.

FIGS. 12 and 13 illustrate, respectively, pump output curves for using differential pressure controls without and with temperature compensation for viscosity correction. Without temperature compensation as shown in FIG. 12, as ambient temperature decreased overnight (after 5 pm and remaining so after 5 am) the actual pump stroke volume decreased. In contrast, in a temperature compensated system the stroke volume remains nearly constant despite the same overnight temperature decreases. This comparison illustrates how an EK pump with differential pressure control and temperature compensation may be used to delivery nearly constant pump stroke volumes even as the temperature of the delivery fluid changes.

In one embodiment, temperature compensation is accomplished according to a method similar to that of FIG. 3 and method 300. If the temperature reading remains within a selected range then no compensation is provided. If temperature varies from the predetermined temperature then the controller will adjust the pump on duration to compensate as appropriate.

The information provided by the differential pressure control system may be used to provide other functions to enhance the performance of the EK pump. Examples of other functions include diagnostic analysis of one or more components in the system or error detection in system operation. This performance information may be provided from any of a number of sources internal and external to the pump system. In one specific example, diagnostic and or error detection information and remedial actions are obtained from the analysis, comparison or processing of pressure sensor data (i.e., see FIG. 4). The pressure sensor data may be analyzed on a per stroke basis, using pump stroke averages, using intermittent stroke data (i.e., stroke data taken on some time interval or stroke number interval) or on other circumstances suited to the diagnostic or error detection sought.

In terms of a specific example of system component failure, consider the inlet and outlet check valves. Possible failure modes for a valve are stuck open or stuck closed. In the case of stuck open, the peak pressure in the chamber will be less than average. In this case, the memory of the controller may contain computer readable instructions for recording and comparing peak chamber pressure from stroke to stroke, every other stroke or some other interval or intermediate monitoring rate. If the comparison of peak pressure indicates repeated lowered peak readings then the controller may take action to notify a user of the likely malfunction. Actions the controller make range from alarm indications with lights, sounds or electronic notifications to stopping pump operations or inhibiting pump operations until the condition is cleared. The system may respond in a similar way to the case of a check valve being stuck closed. In this case, the system will read chamber peak pressure as higher than normal or higher than the average peak pressure. In much the same way, the controller may contain additional instructions in memory for notifying the user or altering system performance in light of the component failure.

In still another embodiment, the pressure sensor data may be used to detect an occlusion. In this instance, the controller memory may include instructions in computer readable code for adjusting pump operations to accommodate or compensate for the occlusion, adjust pump operations to attempt to clear the occlusion, notify the user of the possible occlusion, cease pump operations or combinations of any of the above.

In one specific example, the output of PS2 (154) in FIG. 9 provides an indication of back pressure acting on the system. The controller may contain computer readable instructions to add stroke time in anticipation of pumping against a certain back pressure. Alternatively, the controller may signal an alarm or cease pump operations if a back pressure above a threshold value is detected. A two pressure sensor configuration such as in FIG. 1 may also be used to detect component failure. If the pump drive signal is on and there is no difference in the signals from PS1/PS2 then the controller may contain instructions to indicate this abnormal condition. The lack of a pressure difference may indicate.

In another specific example, during application of a reverse drive voltage to run the pump for charge balance a pressure sensor(s) on the chamber and/or reading within the system check valves decreases or becomes negative. Pressure sensor readings such as these are a likely indication that one or both check valves may have failed. The controller may contain computer readable instructions to cease operations or sound an alarm or indication if this abnormal condition is detected. Back pressure compensation may be handled as discussed above and most directly by placing one pressure sensor beyond the outlet check valve (i.e., see the configuration in FIG. 9) and reading PS2 pressure during the pump cycle when the outlet check valve 144 is closed. Occlusion detection may be provided by one or more indications of pump flow or pump operation with an accompanying increase in chamber pressure without a corresponding indication of delivery fluid flow.

In still other alternative embodiments, the result or outcome of one or more error or diagnostic routines may be used to adjust the voltage applied to the pump, the time on duration of the voltage or other suitable operational parameters using methods similar to those described above and with regard to FIGS. 3A and 3B. In this respect, adjusting the voltage applied to the pump would occur before or after stroke delivery. This type of adjusting refers to the use of 4 volts in one stroke and then when circumstances in the pumping system change a different value other than 4 volts may be used. For example, one pump delivery profile may have a number of strokes delivered at 3 volts. Thereafter, based on a change in system parameters or pump stroke voltage may be increased to 5 v on a subsequent stroke.

EXAMPLES

FIG. 14 illustrates a graph of two square wave pump control signals and a corresponding pressure sensor trace from a single pressure sensor differential pressure control system. In this illustrative example, the differential pressure control system would utilize data from the single pressure sensor output (i.e., the integral of the trace curve for a given pump drive signal) to determine stroke volume. A single pressure sensor system configuration is illustrated above in FIG. 6. In this example, the pump drive signal is a constant voltage of about 2.7 volts. The base line pressure sensor output signal is about 75 mv. The duration of the first pulse (t1) is 860 ms. In this example, the pressure sensor output is read every 4 ms. The system controller includes computer readable instructions to begin integrating the pressure sensor readings when the pump drive signal is applied and to continue to integrate until the pressure sensor output voltage decreases below a determined value. Typically, the value would be once the output signal indicates that the system has returned to base pressure (here at a sensor voltage of 75 mv). Thereafter, the obtained integral values are converted to volume and then compared to the target flow. It is to be appreciated that the integral values may be calculated in real-time as the stroke progresses. This real-time stroke volume calculation may be used as a pump off trigger signal back to the controller to stop the flow of power to the EK engine. In this example, the volume delivered during t1 was calculated tilizing the single sensor output values and determined to be over the target amount per stroke. As a result, the subsequent constant voltage pump drive signal is adjusted to be of shorter duration. In this illustration the amount of correction is 36 ms. In this example, t2—the subsequent pump stroke duration—is reduced by 36 ms to a new pump on duration of 824 ms.

FIG. 15 illustrates a graph of two square wave pump control signals and a corresponding pressure sensor traces from a two pressure sensor differential pressure control system. In this illustrative example, the differential pressure control system would utilize data from the difference between the two pressure sensor outputs (i.e., the integral of the trace curve for a given pump drive signal) to determine stroke volume. Two pressure sensor configurations are illustrated above in FIGS. 2 and 10. In this example, the pump drive signal is a constant voltage of about 2.7 volts. The base line pressure sensor output signal is about 50 mv. The duration of the first pulse (t1) is 750 ms. In this example, the pressure sensor output is read every 4 ms. The system controller includes computer readable instructions to begin integrating the differences between the two pressure sensor readings when the pump drive signal is applied and to continue to integrate those differences until the pressure sensor output voltage decreases below a determined value. Typically, the value would be once the output signal indicates that the system has returned to base pressure (here at a sensor voltage of 50 mv). Thereafter, the obtained integral values are converted to volume and then compared to the target flow. It is to be appreciated that the integral values may be calculated in real-time as the stroke progresses. This real-time stroke volume calculation may be used as a pump off trigger signal back to the controller to stop the flow of power to the EK engine. It is to be appreciated that the integral values may be calculated in real-time as the stroke progresses. This real-time stroke volume calculation may be used as a pump off trigger signal back to the controller to stop the flow of power to the EK engine. is to be appreciated that the integral values may be calculated in real-time as the stroke progresses. This real-time stroke volume calculation may be used as a pump off trigger signal back to the controller to stop the flow of power to the EK engine. The volume delivered during t1 was calculated utilizing the dual sensor output values and determined to be under the target amount per stroke. As a result, the subsequent constant voltage pump drive signal is adjusted to be of longer duration. In this illustration the amount of correction is 36 ms. In this example, t2—the subsequent pump stroke duration—is increased by 36 ms to a new pump duration of 786 ms.

The pressure signal traces in FIGS. 14 and 15 also illustrate an additional aspect of the EK pump control system. Both sets of pressure traces indicate that there is a pressure decay after the pump drive voltage goes to zero (i.e., pump drive signal is OFF). This decay curve extends from the point where the pressure output crosses the voltage off line until it reaches the base line output of 75 mv (FIG. 14) and 50 mv (FIG. 15). The areas in each are different with FIG. 14 being larger than FIG. 15. Depending upon the pump system requirements and operating conditions, these remaining flow indications or additional volumes may or may not be significant. If not significant, then the system will ignore them. If significant, then the system can compensate for this type of error using the techniques described herein. The amount of error introduced by this part of the pressure trace (and resulting volume it represents) will result in different outcomes for the determined stroke volume (see FIG. 3A step 210 and FIG. 3B step 310).

If the pressure trace information beyond the pump off signal is not consequential, then the integral period or volume calculation period may stop when the pump off signal occurs. If the pressure trace information beyond the pump off signal is consequential or is to be considered within the stoke compensation scheme, then there are at least two ways to account for this condition. One way to compensate for this type of possible variation is to extend the integral calculation time or volume calculation time for a time period beyond the end of the pump off signal. In one exemplary embodiment, the additional integration time is about 50 ms beyond the pump off signal. Another way to compensate for this type of possible variation is to extend the integral calculation or volume calculation period not by time but instead until the pressure sense voltage drops below a threshold value. Once the pressure sense voltage reaches or exceeds the desired threshold value, then the integral calculation or volume determination time will end.

FIG. 16 is a table with exemplary correction factors as applied to a range of stroke durations. This table illustrates the high degree of precision fluid delivery and correction capabilities provided by the EK pump control schemes described herein. In this example, the pump durations are pre-set amounts of 4 milliseconds (ms), 8 ms, 16 ms and 32 ms. The pump stroke times are selected for typical values for the exemplary chambers described above. The stroke times of 300 ms, 500 ms, 800 ms and 1000 ms are listed. The percentage correction listed corresponds to the amount of correction time to the total stroke duration. For example, a 16 ms correction time represents a 5.3% correction of a 300 ms stroke. An 8 ms correction time represents a 0.8% correction of a 1000 ms stroke.

FIG. 17 is an exemplary corrections value table for a typical pumping system as described herein. The information shown in FIG. 17 may be used as part of the methods 200, 300 described above such as part of steps 230, 330 respectively. The EK pump operates as described above with a differential pressure measurement system utilizing a flow restrictor tube with a length of about 1 inch and an inner diameter of 0.007 inches. In this illustrative example, the pump control system is set with a tolerance of 200 or a value that is 2% of target value. The target integral value is 5000 based on the pressure curves and signals used to generate the curves in FIGS. 14 and 15. The correction value is determined by subtracting the target integral from the measured DPI and then dividing that value by the tolerance value. The tolerance value is a number used to represent the accuracy desired by the system. This is generally set as a percentage value of a pump stroke volume. In this example, the tolerance value is 200. Measured DPI refers to the measured differential pressure integral obtained during the pump stroke as an indication of delivery fluid volume during the stroke. The magnitude of the correction value determines the amount of stroke duration adjustment for the subsequent stroke. The sign of the correction value determines if a subsequent stroke duration is increased (negative correction value result) or decreased (positive correction value result). If the correction value is less than 1, then there is no correction needed. If the correction value is between 1 and 2, then a 4 ms correction time is used. If the correction value is between 2 and 3, then an 8 ms correction time is used. If the correction value is between 3 and 4, then a 16 ms correction time is used. If the correction value is greater than 4, then a 32 ms correction time is used.

Additional details of an exemplary pump controller are described in co-pending and commonly owned U.S. Provisional Patent Application No. 61/482,889, entitled “GEL COUPLING FOR ELECTROKINETIC DELIVERY SYSTEMS,” filed May 5, 2012 and its corresponding U.S. Non-provisional patent application Ser. No. ______, entitled “GEL COUPLING FOR ELECTROKINETIC DELIVERY SYSTEMS,” filed herewith. While described as a modular system having 1100, 1200, the two may be combined into a single system as described above. In addition, the EK pump, pressure sensors, differential pressure system, and controller may be provided in a single housing having a display 1205. FIG. 18 illustrates a control module 1200 configured to apply the pump drive signals, receive and process signals from sensors and other functions to control the operation of an EK pump system as described herein. The control module 1200 can include a power source, such as a battery 1203, for supplying the voltage, and a circuit board 1201 including the circuitry to control the application of voltage to the pump module. The control module can further include a display 1205 to provide instructions and/or information to the user, such as an indication of flow rate, battery level, operation status, and/or errors in the system. In addition the display 1205 may be used to provide a GUI input screen for a user as well as provide information about total volume delivery progress or system status. An on-off switch 1207 can be located on the control module to allow the user to switch the control module on and off. The display 1205 also acts as user input device in communication with the computer controller. The computer controller is also adapted and configured to provide and receive signals from the user input device.

Referring to FIG. 19, the circuit board in the control module 1200 includes voltage regulators 1301, an H-bridge 1303, a microprocessor 1305, an amplifier 1307, switches 1309, and communications 1311. Electrical connections 1310 between the components of the control module 1200 and components of the pump module 1100 enable the control module 1200 to run the pump module 1100. While described as separate for purposes of modular design aspects, it is to be appreciated that the separate, modular aspects of 1100, 1200 may be combined into a single pumping system. The control module can provide between 1 and 20 volts, such as between 2 and 15 volts, for example 2.6 to 11 volts, specifically 3 to 3.5 volts, and up to 150 mA, such as up to 100 mA, to the pump module 1100 depending upon pump configuration.

In use, the batteries 1203 supply voltage to the voltage regulators 1301. The voltage regulators 1301, under direction of the microprocessor 1305, supply the required amount of voltage to the H-bridge 1303. The H-Bridge 1303 in turn supplies voltage to the EK engine 1103 to start the flow of fluid through the pump. The amount of fluid that flow through the pump can be monitored and controlled by the pressure sensors 1152, 1154. Signals from the sensors 1152, 1154 to the amplifier 1307 in the control module can be amplified and then transmitted to the microprocessor 1305 for analysis. Using the pressure feedback information, the microprocessor 1305 can send the proper signal to the H-bridge to control the amount of time that a pump drive signal, such as a constant voltage, is applied to the engine 1103. The switches 1309 can be used to start and stop the engine 1103 as well as to switch between modes of pump module operation, e.g., from bolus to basal mode. The communications 1311 can be used to communicate with a computer (not shown), which can be used for diagnostic purposes and/or to program the microprocessor 1305. In addition or alternatively, the communication 1311 may be configured to provide wired or wireless access to the system 1100/1200.

As shown in FIG. 19, the pump module 100 and the control module 1100 can have at least eight electrical connections extending there between. A positive voltage electrical connection 1310 a and a negative voltage electrical connection 1310 b can extend from the H-bridge 1303 to the engine 1103 to supply the appropriate voltage. Further, an s+ electrical connection 1310 c, 1310 g and an s− electrical connection 1310 d, 1310 h can extend from sensors 1152, 1154, respectively, such that the difference in voltage between the s+ and s− connections can be used to calculate the applied pressure. Moreover, a power electrical connection 1310 e can extend from the amplifier 1307 to both sensors 1152, 1154 to power the sensors, and a ground electrical connection 1310 f can extend from the amplifier 1307 to both sensors 1152, 1154 to ground the sensors. Sensors in the above description may be any of the pressure sensors or other appropriate differential pressure sensors or other control or performance systems utilized in the operation of the EK pump control schemes described herein.

In another alternative embodiment of an electrokinetic pump fluid delivery system, there is a system having an electrokinetic pump in communication with an outlet chamber, a reservoir in communication with the outlet chamber; and a differential pressure flow control system in communication with the outlet chamber. There is provided in accordance with the disclosure above a control system for the delivery system implemented using an electronic controller. The controller is in communication with the electrokinetic pump and the differential pressure flow control system as suited to the specific components thereof. The instructions in the memory of the controller may also include those adapted and configured for communication to and from a differential pressure control system. Such communication includes instructions for the specific components of a differential pressure system including power, control, instructions, data, or other signaling turning components on or off, calibration of said components. Examples of specific components may include those associated with a venturi flow meter, an orifice flow meter, or a flow nozzle flow meter.

The memory of the controller or suitable memory in communication with or accessible to the controller contains computer readable instructions to determine or retrieve data relating to, for example, a pump drive signal, a constant voltage value, a constant current value, a pump stroke time based a correction factor. In one aspect, there is a time based correction factor is based upon a value in a look up table programmed into or accessible to an electronic memory of the computer controller. Still further, a correction factor may be related to a number of different variables or system conditions as described above. The correction factor may be, for example, provided or determined in relation to an input signal to the controller from the electrokinetic pump and an input signal to the controller from the differential pressure flow control system. As such, the electronic memory accessible to the controller may include or be programmed to include, for example, a time based correction factor is based upon a feedback control scheme. Additionally or alternatively, the electronic memory of the computer controller is programmed for or has access separately or in any combination to: (a) a proportional feedback control scheme; (b) a proportional and integral feedback control scheme; and (c) a proportional, integral and derivative feedback control scheme.

Those of ordinary skill will appreciate that the various processing steps, comparisons, methods, techniques, signal processing and component specific operations performed by a controller are provided to the controller or contained within electronic memory accessible to the controller in the form of appropriate computer readable code. Similarly, the various diagnostic routines, abnormal condition detectors, functional indicators and pump control schemes and other operational considerations described in this patent application are also stored in an appropriate computer readable code within the memory of or accessible to the controller. In one specific example, the computer readable instructions in the memory of the computer controller implement control schemes for pump cycle duration based on computations made based at least in part on a differential pressure flow control (instructions to adjust the pump duration based on a calculated stroke time adjustment), including techniques described herein for stroke duration response is calculated, as well as the tables, files or data relating to those embodiments where the stroke response adjustment is selected one of a set of pre-selected stroke durations.

As for additional details pertinent to the present invention, materials and manufacturing techniques may be employed as within the level of those with skill in the relevant art. The same may hold true with respect to method-based aspects of the invention in terms of additional acts commonly or logically employed. Also, it is contemplated that any optional feature of the inventive variations described may be set forth and claimed independently, or in combination with any one or more of the features described herein. Likewise, reference to a singular item, includes the possibility that there are plural of the same items present. More specifically, as used herein and in the appended claims, the singular forms “a,” “and,” “said,” and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation. Unless defined otherwise herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The breadth of the present invention is not to be limited by the subject specification, but rather only by the plain meaning of the claim terms employed.

It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby. 

1. A method of controlling the output of an electrokinetic pump to deliver a target stroke volume, comprising: Applying a pump drive signal to the electrokinetic pump for a pump stroke time duration is about one second; Determining a volume of a delivery fluid pumped during the pump stroke time duration; Comparing the volume of the delivery fluid pumped to the target stroke volume; Generating a new time interval for applying the pump drive signal to the electrokinetic pump based upon the comparing step; and Applying the pump drive signal to the electrokinetic pump for the new time interval.
 2. The method of controlling the output of an electrokinetic pump according to claim 1 wherein the difference between the new time interval and the pump stroke time duration is no more than 100 ms.
 3. The method of controlling the output of an electrokinetic pump according to claim 1 wherein the new time interval is a time duration that maintains the electrokinetic pump within the reversible faradaic limits of the electrokinetic pump components.
 4. The method of controlling the output of an electrokinetic pump according to claim 1 wherein the pump stroke time duration is selected to remain within the reversible faradic operating parameters of the electrokinetic pumps.
 5. The method of claim 1 wherein the generating a new time interval is based in part on a temperature compensation related to a delivery fluid temperature.
 6. The method of controlling the output of an electrokinetic pump according to claim 1 wherein the determining a volume step includes the use of a differential pressure flow technique.
 7. The method of controlling the output of an electrokinetic pump according to claim 6 wherein the differential pressure flow technique is based on an input from at least one pressure sensor in communication with the pump outlet.
 8. The method of controlling the output of an electrokinetic pump according to claim 6 wherein the differential pressure flow technique uses a flow restrictor and is based on an input from at least one pressure sensor.
 9. The method of claim 6 wherein the determining the volume is based on a comparison of two differential pressure signals after the initial applying a pump drive signal step.
 10. The method of claim 6 wherein the determining the volume is based on an integral of a pressure sensor during the applying a pump drive signal step.
 11. The method of claim 6 wherein the determining the volume is based on an integral a difference between two pressure sensors during the applying a pump drive signal step.
 12. The method of claim 6 wherein the determining the volume is based on an estimated delivery condition read from a pressure sensor during the applying a pump drive signal step.
 13. The method of claim 12 wherein the duration of the applying a pump drive signal is adjusted based on the estimated delivery condition read from a pressure sensor during the applying a pump drive signal step.
 14. The method of controlling the output of an electrokinetic pump according to claim 6 wherein the differential pressure flow measurement technique uses input from a pair of pressure sensors.
 15. The method of controlling the output of an electrokinetic pump according to claim 9 wherein one of the pressure sensors is in communication with the pump outlet.
 16. The method of controlling the output of an electrokinetic pump according to claim 9 wherein one of the pressure sensors is positioned to indicate backpressure acting on the output of the electrokinetic pump.
 17. The method of controlling the output of an electrokinetic pump according to claim 1 further comprising: before the applying a pump drive signal for the new time interval, applying a pump drive signal of opposite polarity to the pump drive signal used in the initial applying a pump drive signal step, wherein the duration of the applying a pump drive signal of opposite polarity is the same as the pump stroke time duration.
 18. The method of controlling the output of an electrokinetic pump according to claim 1 further comprising: after applying the pump drive signal for the new time interval, applying a pump drive signal of opposite polarity to the pump drive signal used in the applying a pump drive signal for the new time interval step, wherein the duration of the applying a pump drive signal of opposite polarity is the same as the new time interval duration.
 19. The method of controlling the output of an electrokinetic pump according to claim 1 wherein the pump drive signal during the applying steps is a constant voltage.
 20. The method of controlling the output of an electrokinetic pump according to claim 1 wherein the pump drive signal during the applying steps is a constant current.
 21. The method of claim 1 wherein the duration of the applying a pump drive signal is adjusted based on the estimated delivery condition read from a pressure sensor just prior to the applying a pump drive signal step.
 22. The method of claim 1 further comprising: decrementing a total volume delivery counter according to the result of the determining a volume of a delivery fluid pumped step.
 23. The method of claim 1 further comprising: incrementing a total volume delivery counter according to the result of the determining a volume of a delivery fluid pumped step.
 24. The method of claim 23 further comprising: generating a pump stop signal when the result of the determining a volume of a delivery fluid pumped step is the last delivery increment of the total volume delivery counter.
 25. The method of claim 23 further comprising: generating a pump stop signal when the result of the determining a volume of a delivery fluid pumped step is the last delivery decrement of the total volume delivery counter.
 26. A system for delivery of fluid, comprising: An electrokinetic pump configured to deflect a diaphragm in an outlet chamber, the outlet chamber having an inlet and an outlet; A first check valve in communication with the inlet; A second check valve in communication with the outlet; A pressure sensor positioned to indicate a pressure within the system between the first check valve and the second check valve; and A computer controller in communication with the electrokinetic pump and the pressure sensor containing computer readable instructions to determine an output of the electrokinetic pump based at least in part on a signal from the pressure sensor and to generate a stroke time delivery adjustment after each deflection of the diaphragm into the outlet chamber.
 27. The system of claim 26 further comprising: another pressure sensor and a flow restrictor wherein, the pressure sensor is positioned to indicate the pressure of the outlet chamber, the flow restrictor is positioned between the outlet chamber outlet and the second check valve and the another pressure sensor is positioned to indicate a pressure within the system between the flow restrictor and the second check valve.
 28. The system of claim 26 further comprising: a reservoir containing a delivery fluid and having an outlet in communication with the outlet chamber inlet.
 29. The system of claim 26 further comprising: a delivery conduit in communication with the outlet chamber outlet.
 30. The system of claim 26 further comprising: a flow restrictor wherein, the flow restrictor is positioned between the outlet chamber outlet and the second check valve and the pressure sensor is positioned to indicate a pressure within the system between the flow restrictor and the outlet chamber.
 31. The system of claim 26 further comprising: another pressure sensor and a flow restrictor wherein, the flow restrictor is positioned between the second check valve and a delivery conduit and the pressure sensor is positioned to indicate the pressure downstream of the flow restrictor in the delivery conduit.
 32. The system of claim 26 the system further comprising: a user input device in communication with the computer controller wherein the computer controller is adapted and configured to provide and receive signals from the user input device. 